Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2

Noriyuki Akahoshi, Yasuki Ishizaki, Hiroki Yasuda, Yoshiya L. Murashima, Toshikazu Shinba, Kaoru Goto, Toshiyuki Himi, Jerold Chun, Isao Ishii

研究成果: Article

21 引用 (Scopus)

抄録

The diverse physiological effects of sphingosine 1-phosphate (S1P) are mostly mediated by its five cognate G protein-coupled receptors, S1P 1-S1P 5, which have attracted much attention as future drug targets. To gain insight into S1P 2-mediated signaling, we analyzed frequent spontaneous seizures in S1P 2-deficient (S1P 2 -/-) mice obtained after several backcrosses onto a C57BL/6N background. Full-time video recording of 120 S1P 2 -/- mice identified 420 seizures both day and night between postnatal days 25 and 45, which were accompanied by high-voltage synchronized cortical discharges and a series of typical episodes: wild run, tonic-clonic convulsion, freezing, and, occasionally, death. Nearly 40% of 224 S1P 2 -/- mice died after such seizures, while the remaining 60% of the mice survived to adulthood; however, approximately half of the deliveries from S1P 2 -/- pregnant mice resulted in neonatal death. In situ hybridization revealed exclusive s1p 2 expression in the hippocampal pyramidal/granular neurons of wild-type mice, and immunohistochemistry/microarray analyses identified enhanced gliosis in the whole hippocampus and its neighboring neocortex in seizure-prone adult S1P 2 -/- mice. Seizure-prone adult S1P 2 -/- mice displayed impaired spatial working memory in the eight-arm radial maze test and increased anxiety in the elevated plus maze test, whereas their passive avoidance learning memory performance in the step-through test and hippocampal long-term potentiation was indistinguishable from that of wild-type mice. Our findings suggest that blockade of S1P 2 signaling may cause seizures/hippocampal insults and impair some specific central nervous system functions.

元の言語English
ページ(範囲)659-665
ページ数7
ジャーナルEpilepsy and Behavior
22
発行部数4
DOI
出版物ステータスPublished - 2011 12

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Memory Disorders
Short-Term Memory
Seizures
Anxiety
sphingosine 1-phosphate
Spatial Memory
mouse sphingosine-1-phosphate receptor-2
Tonic-Clonic Epilepsy
Avoidance Learning
Video Recording
Gliosis
Long-Term Potentiation
Pyramidal Cells
Neocortex
Microarray Analysis
G-Protein-Coupled Receptors
Exercise Test
Freezing
In Situ Hybridization
Hippocampus

ASJC Scopus subject areas

  • Clinical Neurology
  • Behavioral Neuroscience
  • Neurology

これを引用

Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2. / Akahoshi, Noriyuki; Ishizaki, Yasuki; Yasuda, Hiroki; Murashima, Yoshiya L.; Shinba, Toshikazu; Goto, Kaoru; Himi, Toshiyuki; Chun, Jerold; Ishii, Isao.

:: Epilepsy and Behavior, 巻 22, 番号 4, 12.2011, p. 659-665.

研究成果: Article

Akahoshi, N, Ishizaki, Y, Yasuda, H, Murashima, YL, Shinba, T, Goto, K, Himi, T, Chun, J & Ishii, I 2011, 'Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2', Epilepsy and Behavior, 巻. 22, 番号 4, pp. 659-665. https://doi.org/10.1016/j.yebeh.2011.09.002
Akahoshi, Noriyuki ; Ishizaki, Yasuki ; Yasuda, Hiroki ; Murashima, Yoshiya L. ; Shinba, Toshikazu ; Goto, Kaoru ; Himi, Toshiyuki ; Chun, Jerold ; Ishii, Isao. / Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2. :: Epilepsy and Behavior. 2011 ; 巻 22, 番号 4. pp. 659-665.
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AU - Shinba, Toshikazu

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